Kawabata H, Nakamaki T, Ikonomi P, Smith R D, Germain R S, Koeffler H P
Division of Hematology/Oncology, Department of Medicine, Cedars-Sinai Medical Center, Burns and Allen Research Institute, University of California, Los Angeles, School of Medicine, 90048, USA.
Blood. 2001 Nov 1;98(9):2714-9. doi: 10.1182/blood.v98.9.2714.
Iron is essential for cell proliferation, heme synthesis, and a variety of cellular metabolic processes. In most cells, transferrin receptor-mediated endocytosis is a major pathway for cellular iron uptake. Recently, transferrin receptor 2 (TfR2), another receptor for transferrin, was cloned. High levels of expression of TfR2 messenger RNA (mRNA) occur in the liver, as well as in HepG2 (a hepatoma cell line) and K562 (an erythroid leukemia cell line). In this study, TfR2 mRNA expression was analyzed in hematological cell lines, normal erythroid cells at various stages of differentiation, and leukemia and preleukemia cells. High levels of TfR2 expression occurred in all of the erythroid cell lines that were examined. Erythroid-specific expression of TfR2 protein in bone marrow cells was confirmed by immunohistochemical staining. Expression of TfR2 mRNA was high in normal CD34(+) erythroid precursor cells, and levels decreased during erythroid differentiation in vitro. Levels of expression of TfR2-alpha mRNA were significantly higher in erythroleukemia (M6) marrow samples than in nonmalignant control marrow samples. In addition, relatively higher levels of TfR2-alpha mRNA expression occurred in some samples of myelodysplastic syndrome that had erythroid hyperplasia in bone marrow, acute myelogenous leukemia M1, M2, and chronic myelogenous leukemia. Expression profiles of normal members of the erythroid lineage suggest that TfR2-alpha may be a useful marker of early erythroid precursor cells. The clinical significance of TfR2-alpha expression in leukemia cells remains to be determined.
铁对于细胞增殖、血红素合成以及多种细胞代谢过程至关重要。在大多数细胞中，转铁蛋白受体介导的内吞作用是细胞摄取铁的主要途径。最近，转铁蛋白的另一种受体——转铁蛋白受体2（TfR2）被克隆出来。TfR2信使核糖核酸（mRNA）在肝脏以及HepG2（一种肝癌细胞系）和K562（一种红白血病细胞系）中高水平表达。在本研究中，对血液学细胞系、不同分化阶段的正常红系细胞以及白血病和白血病前期细胞中的TfR2 mRNA表达进行了分析。在所检测的所有红系细胞系中均出现了TfR2的高水平表达。通过免疫组织化学染色证实了骨髓细胞中TfR2蛋白的红系特异性表达。正常CD34(+)红系前体细胞中TfR2 mRNA的表达较高，并且在体外红系分化过程中水平降低。红白血病（M6）骨髓样本中TfR2-α mRNA的表达水平显著高于非恶性对照骨髓样本。此外，在一些骨髓有红系增生的骨髓增生异常综合征样本、急性髓性白血病M1、M2以及慢性髓性白血病中，TfR2-α mRNA的表达水平相对较高。红系谱系正常成员的表达谱表明，TfR2-α可能是早期红系前体细胞的一个有用标志物。TfR2-α在白血病细胞中的表达的临床意义仍有待确定。
